Antibiotic use could have effects many years later

Action Points

Frequent antibiotic users were about 50% more likely to be diagnosed with type 2 diabetes (T2DM) compared with infrequent users.

Note that a slightly stronger association was seen with bactericidal and narrow-spectrum antibiotics compared to bacteriostatic and broad-spectrum groups.

Frequent antibiotic users were about 50% more likely to be diagnosed with type 2 diabetes (T2DM) compared with infrequent users, according to a nationwide population-based case-control study in Denmark.

In fact, increased antibiotic use among people who would eventually be diagnosed with T2DM was noted as early as 15 years before their diagnosis, reported a team of investigators led by Kristian Mikkelsen, a PhD student at the University of Copenhagen.

"Although we cannot infer causality from this study, the findings raise the possibility that antibiotics could raise the risk of type 2 diabetes. Another equally compelling explanation may be that people develop type 2 diabetes over the course of years and face a greater risk of infection during that time," Mikkelsen said in a press release.

The investigators combined data from three national public health registries in Denmark. "Virtually all medical care in Denmark is provided by public health authorities, whereby the Danish health registries allow true population-based studies, covering all inhabitants of Denmark," the investigators said.

The research team identified all Danish citizens diagnosed with T2DM from 2000-2012 and compared antibiotic use in this population with an age- and gender-matched control population.

Compared with individuals who filled 0-1 antibiotic prescriptions during the study period, those who filled 5 or more were 53% more likely to develop diabetes (OR 1.53; 95% CI 1.50 to 1.55), the study found.

People who filled 2-4 antibiotic prescriptions also had a significantly higher T2DM risk than the lowest antibiotic users (OR 1.21; 95% CI 1.19 to 1.23).

When T2DM risk was categorized according to antibiotic type, the differences were found to be small. The strongest association was found for narrow-spectrum antibiotics (OR 1.55; 95% CI 1.53 to 1.57) and the weakest association for broad-spectrum antibiotics (OR 1.31; 95% CI 1.29 to 1.34).

"In further analysis, we found that increased exposure to antibiotics among cases was observed for up to 15 years before the type 2 diabetes index date, with a relative exposure rate (case versus controls) that slowly but consistently increased from 1.20 15 years before the index date to 1.35 in the year prior to the index date," Mikkelsen and colleagues said.

"Because different groups of bacteria may have either a positive or negative impact on host energy homeostasis and glucose metabolism, our primary aim of this study was to test the possibility that different antibiotic groups targeting specific gut bacteria classes could induce different effects on the risk for development of type 2 diabetes," the investigators said.

"However, the uniformly increased ORs for type 2 diabetes between groups of antibiotics in our study do not support the idea of one or a few antibiotics with particularly strong metabolic side effects," they said.

The investigators concluded that "our results call for new investigations of the long-term effect of antibiotics on lipid and glucose metabolism and body weight gain. In particular, we suggest investigation of commonly used narrow-spectrum penicillins because these drugs are frequently prescribed and showed the highest OR for type 2 diabetes risk."

"What struck me about this study was there was almost no difference according to the type of antibiotic. To me that's a red flag," George Grunberger, MD, of the Grunberger Diabetes Institute in Bloomfield Hills, Michigan, and president of the American Association of Clinical Endocrinologists, told MedPage Today.

"Every class of antibiotics works differently. They affect different bugs. If you tell me that there was no difference among them that tends to shoot down the theory that these antibiotics are altering gut flora -- unless every class alters it in the same way," Grunberger said.

However, "as with everything else in science, we need studies to show cause and effect," he said.

In the meantime, the apparent antibiotics-T2DM link is another reason physicians should be cautious about over-prescribing antibiotics, Grunberger said.

This research was supported by the Region of Southern Denmark.

The investigators on this study reported financial relationships with a variety of commercial entities, including Novartis, Pfizer, Genzyme, Eli Lilly, Astellas, AstraZeneca, and Boehringer Ingelheim.

George Grunberger reported no relevant financial relationships with industry.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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